Over 1.6 million people live with limb loss in the United States, and 80,000 to 90,000 lower limb amputation surgeries are performed each year in this country alone. Locomotion eases our ability to perform our everyday activities at home, work, and in the community, and it is imperative for individuals who undergo lower extremity amputations to achieve locomotive levels to maximize quality of life. Early studies on functional capabilities of individuals with lower extremity amputations (ILEA) found that the most difficult physical activity was running. Recent developments of running-specific prostheses (RSPs) have attracted many ILEA to choose running as their form of cardiovascular exercise and it is likely that the cardiovascular benefits of running reported in prior studies extend to this population. However, the impact forces and mechanical adaptations of running with an RSP may put this group at risk for physical injuries and degenerative joint diseases, as suggested by our preliminary data and previous studies. Our preliminary data on ILEA running show that the ground reaction forces recorded provide asymmetrical loading to the limbs with the intact limb bearing a greater load than the residual limb. This pattern was consistent at different running velocities. Asymmetrical limb loading has been indicated as a risk factor in the development and progression of degenerative joint diseases (DJD), but more specific data, such as adaptations in joint kinetics, are needed to better understand the mechanisms of DJD and overuse injuries. Unfortunately, a very limited number of studies provide insights into more specific mechanisms of joint loading and adaptations made by ILEA during running. Furthermore, no validated biomechanical models currently exist for joint kinetic analyses of ILEA running with RSPs. Our preliminary work has developed such a model and indicates that accurate joint kinetic measurements can be estimated and interpreted. Using this model we propose to assess the force transmission through the lower extremities and the biomechanical adaptations of ILEA running with RSPs. By systematically testing a range of running velocities, we will examine joint kinetic adaptations employed to achieve these velocities to compare and contrast ILEA adaptations to those of able-bodied control subjects. Our central hypothesis is that running with an RSP will cause greater strain on the intact limb of ILEA compared to able-bodied runners as measured by joint kinetic adaptations. The long-term objective of this research program is to characterize ILEA running and use these findings as a scientific foundation to develop RSPs and rehabilitation strategies that minimize the potential for overuse injury while maximizing the health and quality of life for ILEA. PUBLIC HEALTH RELEVANCE: The recent developments in running-specific prostheses (RSPs) have attracted many individuals with low- extremity amputations (ILEA) to running for cardiovascular exercise, and it is likely that the cardiovascular benefits of running reported in previous studies can generalize to ILEA. However, the impact forces and mechanical adaptations of running with an RSP may put this group at risk for physical injuries and degenerative joint diseases. We propose to assess these risks by measuring the force transmission through the lower extremities and biomechanical adaptations of ILEA running with RSPs using biomechanical models developed and validated in our preliminary studies.